mortality/aging
• mice succumb to highly aggressive T cell malignancy with a median lifespan of 169 days
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endocrine/exocrine glands
• the cellularity of the thymus is decreased, with decreased thymocyte numbers
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• 90% of mice develop hematologic malignancy
• most tumors are aggressive T cell lymphomas or leukemias which become disseminated to the spleen
• lymphomas contain whole chromosome 15 duplications
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hematopoietic system
• 90% of mice develop hematologic malignancy
• most tumors are aggressive T cell lymphomas or leukemias which become disseminated to the spleen
• lymphomas contain whole chromosome 15 duplications
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• pro-B cells (CD43+) are increased
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• hematopoiesis is severely impaired
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• the cellularity of the bone marrow is decreased
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• 2-fold elevation in platelets
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• white blood cell counts are reduced in 6-to 8-week-old mice
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• the percentage of peripheral B cells is decreased
• percentage of B lineage cells (B220+) is decreased by roughly 3-fold
• depletion of B cell lineage cells coincides with the onset of Ig gene assembly: whereas pro-B cells (CD43+) are increased, the levels of B220+ cell decrease beginning at the pre-B stage when Ig heavy chain rearrangement commences to the immature B cell stage (CD43-)
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• IgM+ mature B cells are virtually undetectable
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• percentage of myeloid cells (Mac-1+ and Gr-1+) is decreased by roughly 3-fold
• however, levels of erythroid precursors (Ter119+) are unchanged
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• red blood cell numbers are reduced in 6-to 8-week-old mice
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• an increase in copy number of the MRE11 and CHK1 genes on chromosome 9 is detected in thymocytes as early as 4 weeks of age
• MYC amplification on chromosome 15 is detected in thymocytes at 4 weeks of age
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• CD8+ population is elevated in the thymus at 6 weeks of age
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• the percentage of peripheral T cells is decreased
|
• the cellularity of the thymus is decreased, with decreased thymocyte numbers
|
immune system
• 90% of mice develop hematologic malignancy
• most tumors are aggressive T cell lymphomas or leukemias which become disseminated to the spleen
• lymphomas contain whole chromosome 15 duplications
|
• pro-B cells (CD43+) are increased
|
• white blood cell counts are reduced in 6-to 8-week-old mice
|
• the percentage of peripheral B cells is decreased
• percentage of B lineage cells (B220+) is decreased by roughly 3-fold
• depletion of B cell lineage cells coincides with the onset of Ig gene assembly: whereas pro-B cells (CD43+) are increased, the levels of B220+ cell decrease beginning at the pre-B stage when Ig heavy chain rearrangement commences to the immature B cell stage (CD43-)
|
• IgM+ mature B cells are virtually undetectable
|
• an increase in copy number of the MRE11 and CHK1 genes on chromosome 9 is detected in thymocytes as early as 4 weeks of age
• MYC amplification on chromosome 15 is detected in thymocytes at 4 weeks of age
|
• CD8+ population is elevated in the thymus at 6 weeks of age
|
• the percentage of peripheral T cells is decreased
|
• the cellularity of the thymus is decreased, with decreased thymocyte numbers
|
neoplasm
• 90% of mice develop hematologic malignancy
• most tumors are aggressive T cell lymphomas or leukemias which become disseminated to the spleen
• lymphomas contain whole chromosome 15 duplications
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• leukemias contain activating mutation of NOTCH1
• 90% of mice develop hematologic malignancy
• most tumors are aggressive T cell lymphomas or leukemias which become disseminated to the spleen
• tumors show the presence of multiple broad DNA copy number gains and losses, with recurrent copy number variation on chromosomes 9 and 15 and overexpression of MRE11 and CHK1
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
T-cell acute lymphoblastic leukemia | DOID:5603 | J:277750 |